Membrane Transport

Membrane transport **Passive diffusion**

Pharmacology for dummies

• PK is the quantitative study of drug movement in, through and out of the body During these movements a drug has to cross various biological membranes
Study of membrane transport explains how drugs cross biological membranes Pharmacology for dummies

Types of membrane transport

1. Passive diffusion and Filtration 2. Specialized transport a. Carrier transport
Facilitated diffusion
Active transport * Primary active * Secondary active b. Pinocytosis Pharmacology for dummies

Passive diffusion Higher Concentration

Passive diffusion of drug {Higher to lower}

Membrane Pharmacology for dummies

Lower Concentration Passive diffusion

•Down a concentration or electrochemical gradient •Not saturable •No energy required •Lipid soluble & nonionized diffuse better •Ionized drugs pass poorly •Governed by Fick’s law •Ion trapping concept

Passive diffusion and influence of pH • Most drugs are weak electrolytes which partially ionize in aqueous solutions • Unionized drugs diffuse [Absorbed] better • Ionization is pH dependent. Hence absorption is pH dependent • Weakly acidic drugs ionize more in alkaline medium. Hence poorly absorbed in alkaline medium [Eg.Penicillin V, aspirin] • Weakly alkaline drugs ionize more in acidic medium. Hence poorly absorbed in acidic medium [Chloroquine, atropine] • These considerations lead to three implications -On Absorption,Ion trapping and Excretion Pharmacology for dummies

pH and absorption Acidic Drugs Unionized

Absorbed better

Acidic

Alkaline Alkaline Drugs-Unionized

Absorbed better

Note: Irrespective of ionization most of the absorption takes place in the small intestine because of the large surface area Pharmacology for dummies

pH and ion trapping Acidic Drugs Unionized Eg.Aspirin

Gastric cell [Alkaline] Absorbed

Ionized Acidic Medium

Can not diffuse further

Trapped

Pharmacology for dummies

Cell damage

pH and excretion in urine Overdose of Aspirin [Acidic drug] Alkalanize urine [With Na Hco3] Drug ionized Poorly absorbed

Excreted Urine is alkalanized[Na Hco3] or acidified [NH4Cl] to increase excretion of acidic or basic drugs respectively, in overdosage. Pharmacology for dummies

Questions • 1. Discuss with examples implications of pH on drug transport across biological membranes • 2. What are the factors which determine passive diffusion across membranes? • Most important determinant of iontrapping is a. pH across membranes b. Lipid solubility of a drug c. Aqueous solubility of the drug d. None of the above Answer: ‘ a’ Pharmacology for dummies

Questions • In a patient who presented with barbiturate poisoning following drug can be administered to facilitate excretion of barbiturate in urine a. b. c. d.

Ammonium chloride Ascorbic acid Sodium bicarbonate Sodium chloride

Answer: ‘ c ‘. To alkalanize urine which increases ionization and increases excretion. Pharmacology for dummies